effectiveness of belimumab treatment in a subpopulation of systemic lupus erythematosus (sle) patients: a pooled analysis of bliss-52 and bliss-76

Conditions: Systemic Lupus Erythematosus

Summary: this pooled analysis will assess data from the phase 3 belimumab registration studies bliss-52 (aka bel110752) and bliss-76 (aka bel110751). the analysis was pre-planned and agreed prior to the unblinding of either study. the primary objective is to evaluate the impact of belimumab treatment on a more severe subpopulation of systemic lupus erythematosus (sle) subjects from bliss-52 and bliss-76 to aid physicians and payers in decision making. subjects are from the modified intent-to-treat (itt) population defined as randomized subjects who received at least 1 dose of study agent. this more severe subpopulation will have renal, neurological, haematological, or cardiovascular/respiratory organ domain involvement (as defined by a british isles lupus assessment group (bilag) domain score of a, b or c in at least one of the domains) at baseline and anti-double-stranded deoxyribonucleic acid (anti-dsdna) positive (≥ 30 iu/ml) at baseline or low c3 and/or c4 complement relative to the normal range at baseline.


Eligibility criteria:
inclusion criteria * eligible subjects for bliss-52 and bliss-76 included: * clinical diagnosis of systemic lupus erythematosus (sle) according to the american college of rheumatology (acr) criteria * "active" (systemic lupus erythematosus) sle disease, defined as a safety of oestrogen in lupus national assessment (selena) systemic lupus erythematosus disease activity index (sledai) disease activity score of at least 6 at screening * an unequivocally positive antinuclear antibodies (ana) test result, from 2 independent time points within the study screening period or 1 positive historical test result and 1 positive test result during the screening period. ana test results obtained in the screening period were only considered positive if the ana titer ≥ 1:80 and/or anti-dsdna serum antibody was ≥ 30 iu/ml * on a stable sle treatment regimen for at least 30 days prior to day 0, which consisted of any of the following (alone or in combination): prednisone or equivalent (from 0 to 40 mg/day when used in combination with other sle treatment or from 7.5 to 40 mg/day alone), anti-malarials, non-steroidal anti inflammatory drugs (nsaids), or any immunosuppressive therapy (i.e., methotrexate, azathioprine, leflunomide, or mycophenolate calcineurin inhibitors, sirolimus, oral cyclophosphamide, 6-mercaptopurine, or thalidomide). * additional inclusion criteria for the purpose of this analysis: subpopulation of patients from the pooled modified intent-to-treat population from bliss-52 and bliss-76 who have renal, neurological, haematological, or cardiovascular/respiratory organ domain involvement (as defined by a bilag domain score of a, b or c in at least one of the domains) at baseline and 1 of the following: * are anti-dsdna positive (≥ 30 iu/ml) at baseline, or * have low c3 and/or c4 complement relative to the normal range at baseline. exclusion criteria: * key exclusion criteria for bliss-52 and bliss-76 included: * severe active lupus nephritis or central nervous system (cns) lupus * pregnancy * receipt of any b cell target therapy at any time * receipt of an investigational agent within 60 days prior to day 0 for non-biologics and within 1 year for biologics * receipt of abatacept (within 1 year), intravenous (iv) cyclophosphamide (within 6 months), anti-tumor necrosis factor (anti-tnf) therapy, anakinra, iv immunoglobulin (ivig), prednisone \> 100 mg/day, or plasmapheresis within 3 months, or live vaccine within 1 month.

Keywords: pooled analyses quality of life selena sledai sle steroid use responder rate flares belimumab bilag